P1077: RISK OF IMPAIRED OVARIAN RESERVE AND ADVERSE PREGNANCY OUTCOMES AFTER TREATMENT FOR CHILDHOOD HODGKIN LYMPHOMA; THE DCOG LATER-VEVO STUDY.
Authors: Katja Drechsel, Simone Broer, Francis Stoutjesdijk, Jos Twisk, Marleen van den Berg, Cornelis Lambalk, Flora van Leeuwen, Annelies Overbeek, Eline van Dulmen, Gertjan Kaspers, Margreet Veening
Journal: HemaSphere (2023)

Topic: 17. Hodgkin lymphoma - Clinical Background: Childhood Hodgkin Lymphoma (HL) is nowadays highly curable with survival rates over 90%. Chemotherapy and radiation are associated with late adverse effects including risk of reduced ovarian function and –reserve that can substantially affect quality of life in survivorship. With an increasing population of childhood cancer survivors, there is a growing need to increase knowledge on the occurrence and, where possible, prevention of late effects of treatment. Aims: To evaluate the impact of pediatric Hodgkin lymphoma (HL) treatment on clinical reproductive markers and self-reported pregnancy outcomes in a cohort of patients surviving at least 5 years after diagnosis. In addition, we aimed to identify treatment- and diagnosis-related factors associated with impaired reproductive function. Methods: This study, including 84 HL survivors and 798 controls, was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study performed between 2004 and 2014 in which the reproductive ability of female childhood cancer survivors was studied and compared to controls (siblings and females from the general population). The current analysis included all female childhood HL survivors, treated between 1963 and 2002, and controls who provided written informed consent to participate in the LATER-VEVO study. Levels of anti-Müllerian hormone (AMH), FSH, inhibin B, as well as antral follicle counts (AFC) and self-reported (first) pregnancy rates and -outcomes were evaluated And extensive treatment data were collected. Results: HL survivors and controls were aged 29.6 (IQR 19.8-36.6) and 32.7 (IQR 19.7-49.6) years at time of assessment. Median age at HL diagnosis was 13.4 years (IQR 6.4-16.4), with median time since diagnosis of 16.5 (IQR 8.4;36.6) years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000mg/m2 in 56 (67%) female survivors and 14 (17%) survivors received pelvic irradiation. All clinical markers of reproductive function were significantly deteriorated in survivors compared to controls after adjusting for age at time of study, smoking and use of hormonal contraceptives at time of clinical measurement (odds-ratio for low AMH (<P10) 10.1 [95%CI 4.9;20.6]; low AFC (<P10) 4.6 [95%CI 2.1;9.9]; elevated FSH (>10IU/l) 15.3 [95%CI 5.7;41.1], low Inhibin B (<20ng/l) 3.6 [95%CI 1.7;7.7], all p<0.001, 45 survivors and 413 controls). Pregnancy rates and outcomes were not statistically significantly different between survivors and controls. However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P=0.04, 42 survivors and 389 controls) and were at increased risk for a time to pregnancy (TTP) of >12 months (adjusted odds-ratio 2.5 [95% CI 1.1;5.6] in survivors, p=0.031). No significant differences in birth weight or gestational age were observed. Gonadotoxicity was specifically present after treatment with procarbazine and higher CED-score. No clear effect of age at diagnosis was observed. Summary/Conclusion: HL survivors are at risk of impaired ovarian reserve status. However chance to conceive and pregnancy outcomes appear to be reassuring when attempting pregnancy at a relatively young age. Newly diagnosed patients and survivors should be counselled individually with respect to family planning and potential use of fertility preservation methods in survivorship. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic. Keywords: Hodgkin’s lymphoma, Fertility, Childhood, Pregnancy